Convulsive disturbances are typically observed in humans as rapidly alternating contractions and relaxations of muscles which are manifested by irregular movements of the limbs or body and typically accompanied by unconsciousness. The most common cause of convulsions in human adults is epilepsy. Convulsive seizures occur in children from a variety of causes. Convulsions in children may be due to brain damage from birth injuries, or due to dietary deficiencies such as a lack of vitamin D, or due to metabolic disorders such as hypoglycemia or hypokalemia, or due to a sudden body temperature elevation caused by infections such as pneumonia. Convulsions may also be initiated by brain diseases such as meningitis, encephalitis or tumors, and also by conditions brought on by asphyxia or skull fracture.
Certain 1,4-disubstituted piperazines, namely, arylpiperazine-1-oxo-ethylurea have been evaluated for anti-convulsant activity against pentylenetetrazole-induced convulsions, one such compound being 1-[2-(4-phenylpiperazino)-1-oxoethyl]urea [M. Verderame, J. Med. Chem., 9(1), 153-154 (1966)] and another such compound being 1-{2-[4-(p-chlorophenyl)piperazino]-1-oxoethyl}urea [M. Verderame, J. Med. Chem., 11(5), 1090 (1968)]. Other types of substituted carbamides, namely, 1-substituted acetyl-3-aryl carbamides have been evaluated for anti-convulsant activity against pentylenetetrazole-induced seizures, including such compounds as 1-(N-acetylpyrrolidino)-3-aryl carbamides, 1-(N-acetylpiperidino)-3-aryl carbamides and 1-(N-acetylmorpholino)-3-aryl carbamides [S. S. Parmar et al, J. Pharm. Sci., 61(9), 1366-1369 (1972)]. Certain 1-(substituted 2-aminoacetyl benzothiazolyl)-3-arylurea compounds have been evaluated for anticonvulsant properties and for effects of the compounds on pentobarbitone-induced hypnosis in mice, an example of one such compound being 1-(2-aminoacetyl benzothiazolyl)-3-(3-methylphenyl)urea [S. Nagar et al., Indian J. Pharm., 34(2), 45- 47 (1972)]. Other arylpiperazine-1-oxo-ethylurea compounds have been shown both to depress and to stimulate central nervous system activity [V. K. Agarwal et al., J. Prakt. Chem., 312(5), 964-966 (1970)]. Certain 1-indanylurea and 2-indanylurea derivatives have been evaluated for analgesic activity, examples of such compounds being 1-(1-indanyl)-3-(2-dimethylamino-1-oxoethyl)urea [T. Takahashi et al., Japanese Appl. No. 4583 of 29 Oct. 62] and 1-(2-indanyl)-3-(2-dimethylamino-1-oxoethyl)urea [T. Takahashi et al., Yakugaku Zasshi, 86(10), 958-960 (1966)].
Acetamide derivatives have been investigated for various CNS uses. For example, Belgian Patent No. 706,262 describes a class of tricyclic compounds, namely, diphenylenemethane amine and amide derivatives, mentioned for use as anti-convulsants, as well as for anti-depressive, anti-inflammatory and analgesic uses. U.S. Pat. No. 3,821,249 describes another series of tricyclic-type dibenzothiazepin derivatives asserted to possess psychostimulant, anti-depressive, analgesic, anti-tussive, anti-histaminic and gastric anti-secretory properties. U.S. Pat. No. 4,639,468 describes a class of 2-amino-acetamide derivatives, having use in treatment of epilepsy, dyskinesia such as Parkinsonism, memory troubles and psychic disorders such as depression, with mention in particular of the compound diphenylpropylacetamide.
Various urea or acetamide derivative compounds have been investigated for other pharmaceutical uses. Certain glycylurea derivatives, namely, 1-alkyl-3-dialkylglycyl urea compounds, have been evaluated for antibacterial, anti-inflammatory diuretic shistosomiasis and trichomonicidal properties [P. Truitt et al., J. Med. Chem., 13(3), 574 (1970)]. For example, U.K. Patent No. 1,181,673 describes a series of tricyclic xanthen and thiaxanthen urea derivatives having utility in treatment of peptic ulceration. Carcinogenicity studies have been carried out involving a family of N-(9-acridinyl)glycylglycylglycine compounds [R. M. Peck et al, J. Med. Chem., 19 (12), 1422-1423 (1976)]. A family of acridinylglycine derivatives has been reported to have tumor-inhibiting properties [B. Wysocka-Skrzela, Pol. J. Chem., 56 (10-12), 1573-1576 (1982)]. Belgian Patent No. 636,245 describes a family of 2-(.omega.-alkoxycarbonylalkylideneamino)acetamides having pharmaceutical properties.
Diphenylmethylaminoacetic acid derivatives have been described as intermediates or end products of various laboratory-scale synthetic methods, without mention of pharmaceutical utility: For example, a series of N-benzhydrylaminoacetic acid compounds have been synthesized as intermediates for preparation of N-benzhydrylaminoacetic acid esters or derivatives, two such intermediates being 2-(diphenylmethylamino)acetamide and 2-[di-(para-methoxyphenyl)methylamino]acetamide [A. G. de Vazquez et al, Anales Asoc. Quim. Argentina, 60, 501-507 (1972)]. The compound .alpha.-diphenylmethylaminoacetamide was incidentally sythesized as a by-product in a multi-step preparation of a series of 3-oxo-1,2-diazetidinium ylides [E. C. Taylor et al, J. Am. Chem. Soc., 103, 7743-7752 (1981)].
Other types of urea and acetamide derivatives, such as glycinamide compounds, have been described for various purposes. For example, U.S. Pat. No. 2,203,506 describes certain ureidoalkylpyridinium and pyridinium acetyl urea compounds for use as textile treatment materials and shows, in particular, the compound diethylaminoacetyl urea as an intermediate in preparation of these pyridinium compounds. German Patent No. 2,511,311 describes a family of glycinamides for use as fungicides.